Neurofibromatosis, Type I (NF) is associated with significant cognitive morbidity and with neuroanatomical anomalies. Limited evidence, exists concerning flee relation of these two factors or of their natural history. This grant proposal will address the general hypothesis that children and adolescents with NF vary from healthy control subjects in the development of cognitive and academic skills and that this variance is related to the anomalies in their brain development and morphology. There are 3 Specific Aims: 1.) To determine the evolution of cognitive and learning impairment in children and adolescents with NF using individual growth curve analyses. 2.) To determine the natural history of brain anomalies in children and adolescents with NF, including hyperintensities, optic gliomas, megencephaly, and gray/white matter development. 3.) To determine the interaction in the evolution of neuroanatomical and neuropsychological features of NF. These aims will be accomplished with a large sample of children and adolescents with NF (6-16 years old) using neuropsychological tests and qualitative measures of brain morphology. The influence of neuroanatomical features on neuropsychological growth curves will be computed. The results will tell us about the change across time in neuropsychological and neuroanatomical features of NF, the interaction of these two factors, and possible mediating factors and will help explain the underlying neurological basis to learning disabilities in NF and possibly about the relevance of brain morphological features in other populations of children with learning or cognitive impairments. Of great importance to the patients we see on a clinical basis will be the ability to comment on the relevance of brain morphological features in children and adolescents with NF and their learning profiles. In addition, we will be able to answer a common question from parents, teachers, and medical specialists involved with these patients, "Given that a particular child has or doesn't have brain anomalies, and does or does not have learning difficulties, what will this child be like in the future"?